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DRUG:

sapitinib (AZD8931)

i
Other names: AZD8931, AZD-8931, AZD 8931
Associations
Company:
AstraZeneca
Drug class:
EGFR inhibitor, HER2 inhibitor, HER3 inhibitor
Related drugs:
Associations
1m
FOXN3-AS1: A Candidate Prognostic Marker and Epigenetic Target with Immunotherapeutic Implications in Acute Myeloid Leukemia. (PubMed, Curr Med Chem)
Our candidate approach identifies FOXN3-AS1 as a prognostic indicator of survival in AML with a potential immune-related role. The preliminary observations we made on FOXN3-AS1/DNMT1 crosstalk warrant more in-depth invested immunotherapeutic approaches in AML.
Journal • IO biomarker
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GLI2 (GLI Family Zinc Finger 2)
|
cisplatin • Tagrisso (osimertinib) • temozolomide • Jakafi (ruxolitinib) • dactolisib (RTB101) • vinorelbine tartrate • ulixertinib (BVD-523) • sapitinib (AZD8931)
1m
Immune microenvironment modulation following neoadjuvant therapy for oesophageal adenocarcinoma: a translational analysis of the DEBIOC clinical trial. (PubMed, ESMO Open)
OAC may be subdivided into three immune-related subgroups which undergo modulation in response to neoadjuvant therapy with marked suppression of the immune microenvironment in HER2-positive/immune-high tumours.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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HER-2 positive • HER-2 expression • EGFR positive • EGFR negative
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capecitabine • oxaliplatin • sapitinib (AZD8931)
2ms
Copper metabolism-related signature for prognosis prediction and MMP13 served as malignant factor for breast cancer. (PubMed, Heliyon)
Patients with higher CuScores had lower TMB and were more sensitive to Sapitinib and LCL161, while those with lower CuScores might respond better to anti-PD1 therapy. The identified copper metabolism-related gene signature has the potential to predict prognosis and guide clinical treatment for BC. Among these genes, MMP13 may act as a malignant factor in BC.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CEACAM5 (CEA Cell Adhesion Molecule 5) • MAPK1 (Mitogen-activated protein kinase 1) • ATP7A (ATPase Copper Transporting Alpha) • SLC31A1 (Solute Carrier Family 31 Member 1)
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LCL161 • sapitinib (AZD8931)
9ms
Machine learning-based disulfidptosis-related lncRNA signature predicts prognosis, immune infiltration and drug sensitivity in hepatocellular carcinoma. (PubMed, Sci Rep)
Additionally, the high-risk group exhibited higher sensitivity to Afatinib, Fulvestrant, Gefitinib, Osimertinib, Sapitinib, and Taselisib. In conclusion, our study highlighted the potential utility of the constructed DRLPS in the prognosis prediction of HCC patients, which demonstrated promising clinical application value.
Journal • IO biomarker • Machine learning
|
ZNF23 (Zinc Finger Protein 23)
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Tagrisso (osimertinib) • Gilotrif (afatinib) • gefitinib • fulvestrant • taselisib (GDC-0032) • sapitinib (AZD8931)
9ms
Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model. (PubMed, Clin Exp Metastasis)
L-JIMT-1 cells were resistant to all five tyrosine kinase inhibitors tested in vitro (afatinib, erlotinib, lapatinib, sapitinib, and tucatinib). In a mouse model, all three ADCs inhibited the growth of L-JIMT-1 lung metastases compared to a vehicle, but DV and T-DXd more strongly than T-DM1, and DV treatment led to the smallest tumor burden. The L-JIMT breast cancer lung metastasis model developed may be useful in the evaluation of anti-cancer agents for multiresistant HER2-positive advanced breast cancer.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 positive • EGFR expression
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erlotinib • Gilotrif (afatinib) • lapatinib • Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Tukysa (tucatinib) • Aidixi (disitamab vedotin) • sapitinib (AZD8931)
11ms
SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=1460, Active, not recruiting, UNICANCER | Trial completion date: Dec 2023 --> Dec 2024
Trial completion date • IO biomarker • Metastases
|
Avastin (bevacizumab) • Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • paclitaxel • 5-fluorouracil • Koselugo (selumetinib) • capecitabine • cyclophosphamide • Halaven (eribulin mesylate) • Truqap (capivasertib) • fexagratinib (ABSK091) • epirubicin • Caprelsa (vandetanib) • vincristine • vinorelbine tartrate • bicalutamide • mitomycin • vistusertib (AZD2014) • vinblastine • sapitinib (AZD8931)
11ms
Trial completion • IO biomarker • Metastases
|
Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • pemetrexed • Truqap (capivasertib) • fexagratinib (ABSK091) • Orpathys (savolitinib) • Caprelsa (vandetanib) • vistusertib (AZD2014) • sapitinib (AZD8931)
1year
Inhibition of ErbB3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival. (PubMed, Am J Pathol)
ErbB inhibitors (canertinib and sapitinib) or erbB3 knockdown in combination with Src (saracatinib), calmodulin [trifluoperazine (TFP)], or proviral integration site of Moloney murine leukemia kinase (AZD1208) inhibition even more effectively reduces proliferation and survival. Src inhibition (saracatinib), like erbB3 knockdown, prevents these phosphorylation events and when combined with trifluoperazine even more effectively reduces proliferation and survival compared to monotherapy. Our findings implicate erbB3, calmodulin, PIM kinases and Src family members as important therapeutic targets in MPNSTs and demonstrate that combinatorial therapies targeting critical MPNST signaling pathways are more effective.
Journal
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
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saracatinib (AZD0530) • AZD1208 • canertinib (CI-1033) • sapitinib (AZD8931)
over1year
Identification of the novel markers of PPAR signalling affecting immune microenvironment and immunotherapy response of lung adenocarcinoma patients. (PubMed, J Cell Mol Med)
Intriguingly, high-risk patients exhibited a potential heightened sensitivity to immunotherapy and certain drugs, including Gefitinib, Afatinib, Erlotinib, IAP_5620, Sapitinib, LCL161, Lapatinib and AZD3759. The prognosis model based on eight PPAR-related genes has satisfactory prognosis prediction efficiency. Meanwhile, our results can provide direction for future studies in the relevant aspects.
Journal • IO biomarker
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ACSL3 (Acyl-CoA Synthetase Long Chain Family Member 3) • FABP1 (Fatty Acid Binding Protein 1)
|
erlotinib • Gilotrif (afatinib) • gefitinib • lapatinib • Zorifer (zorifertinib) • LCL161 • sapitinib (AZD8931)
almost2years
SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=1460, Active, not recruiting, UNICANCER | Trial completion date: Dec 2022 --> Dec 2023
Trial completion date • IO biomarker • Metastases
|
PD-L1 (Programmed death ligand 1)
|
Avastin (bevacizumab) • Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • paclitaxel • 5-fluorouracil • Koselugo (selumetinib) • capecitabine • cyclophosphamide • Halaven (eribulin mesylate) • Truqap (capivasertib) • fexagratinib (ABSK091) • epirubicin • Caprelsa (vandetanib) • vincristine • vinorelbine tartrate • bicalutamide • mitomycin • vistusertib (AZD2014) • vinblastine • sapitinib (AZD8931)
2years
PANTHER: AZD8931, inhibitor of EGFR, ERBB2 and ERBB3 signalling, combined with FOLFIRI: a Phase I/II study to determine the importance of schedule and activity in colorectal cancer. (PubMed, Br J Cancer)
The combination of pulsed high-dose AZD8931 with FOLFIRI has acceptable toxicity. Further studies of TKI sequencing may establish a role for pulsed use of such agents rather than continuous exposure.
P1/2 data • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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5-fluorouracil • irinotecan • leucovorin calcium • sapitinib (AZD8931)
2years
Comprehensive genome profiling in patients with metastatic non-small cell lung cancer: the precision medicine phase 2 randomized SAFIR02-Lung trial. (PubMed, Clin Cancer Res)
Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in the current study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients.
P2 data • Journal • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1)
|
EGFR wild-type • ALK wild-type
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Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • Truqap (capivasertib) • fexagratinib (ABSK091) • Orpathys (savolitinib) • Caprelsa (vandetanib) • vistusertib (AZD2014) • sapitinib (AZD8931)
over2years
Dual targeting of FGFR3 and ERBB3 enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer. (PubMed, BMC Cancer)
We demonstrate that increased expression of pERBB3 is a key mechanism of adaptive resistance to FGFR inhibitors in FGFR3-fusion driven bladder cancers, and that this also occurs rapidly following FGFR inhibitor treatment. Our findings demonstrate that resistance can be overcome by combination treatment with a pan-ERBB inhibitor and suggest that upfront combination treatment with FGFR and pan-ERBB inhibitors warrants further investigation for FGFR3-fusion harbouring bladder cancers.
Journal
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FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • BAIAP2L1 (BAI1 associated protein 2 like 1)
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FGFR3-TACC3 fusion • FGFR3 fusion • FGFR3-BAIAP2L1 fusion
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Mekinist (trametinib) • Balversa (erdafitinib) • Truseltiq (infigratinib) • Lytgobi (futibatinib) • sapitinib (AZD8931)
over2years
SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=1460, Active, not recruiting, UNICANCER | Trial primary completion date: Dec 2021 --> Dec 2022
Trial primary completion date • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
Avastin (bevacizumab) • Lynparza (olaparib) • cisplatin • carboplatin • Imfinzi (durvalumab) • gemcitabine • paclitaxel • 5-fluorouracil • Koselugo (selumetinib) • capecitabine • cyclophosphamide • Halaven (eribulin mesylate) • Truqap (capivasertib) • fexagratinib (ABSK091) • epirubicin • Caprelsa (vandetanib) • vincristine • vinorelbine tartrate • bicalutamide • mitomycin • vistusertib (AZD2014) • vinblastine • sapitinib (AZD8931)
over2years
Sorting nexin-dependent therapeutic targeting of oncogenic epidermal growth factor receptor (AACR 2022)
Only transformed lines expressing wildtype EGFR responded to cSNX1.3, while mutant EGFR and normal cells responded better to the EGFR kinase inhibitor (Sapitinib). Phenotypically, cSNX1.3 inhibits EGF-, NRG-, and HGF-dependent migration, but not HA-dependent migration. Together, these data indicate that targeting retrotranslocation of EGFR may be a potent therapeutic for RTK-active cancer.
Late-breaking abstract • PARP Biomarker
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EGFR (Epidermal growth factor receptor) • TGFA (Transforming Growth Factor Alpha)
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EGFR mutation • EGFR expression • EGFR wild-type • EGFR H1975
|
sapitinib (AZD8931)
almost3years
Experiences of running a stratified medicine adaptive platform trial: Challenges and lessons learned from 10 years of the FOCUS4 trial in metastatic colorectal cancer. (PubMed, Clin Trials)
Of the 20 drug combinations that were explored for inclusion in the platform trial, three molecularly targeted sub-trials were activated: FOCUS4-D (February 2014-March 2016) evaluated AZD8931 in the BRAF-PIK3CA-RAS wildtype subgroup; FOCUS4-B (February 2016-July 2018) evaluated aspirin in the PIK3CA mutant subgroup and FOCUS4-C (June 2017-October 2020) evaluated adavosertib in the RAS+TP53 double mutant subgroup. FOCUS4-N was active throughout and evaluated capecitabine monotherapy versus a treatment break...Adaptive stratified medicine platform studies are feasible in common cancers but present challenges. Our stakeholder feedback has helped to inform how these trial designs can succeed and answer multiple questions efficiently, providing resource is adequate.
Journal
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
|
TP53 mutation • PIK3CA mutation • RAS wild-type
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capecitabine • adavosertib (AZD1775) • aspirin • sapitinib (AZD8931)
over3years
SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients (clinicaltrials.gov)
P2, N=999, Active, not recruiting, UNICANCER | Trial completion date: Feb 2021 --> Dec 2023
Clinical • Trial completion date • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • pemetrexed • Truqap (capivasertib) • fexagratinib (ABSK091) • Orpathys (savolitinib) • Caprelsa (vandetanib) • vistusertib (AZD2014) • sapitinib (AZD8931)
over3years
[VIRTUAL] Identification of pathways that enhance cell death in NOTCH1-mutant HNSCC (AACR 2021)
We combined the resulting 74 drugs with PI3K inhibitors, bimiralisib (0-1µM) or copanlisib (FDA approved, 0-100nM), for 72 h. Synergistic effects from these combinations were assessed using Bliss, HAS, Zip, and Loewe models. Trametinib (MEK inhibitor) and copanlisib were synergistic with the combination leading to 0.90 fraction of cells affected at concentrations of 30nM and 100nM respectively...Likewise, low concentrations of inhibitors of EGFR (10nM afatinib, 50nM AZ5104), HER2 (25nM sapitinib, 10nM poziotinib), and PLK1 (50nM BI2536, 50nM volasertib) were both effective and additive to synergistic with PI3K inhibitors...The identified pathways may give us insight into mechanisms of resistance. If validated, these combinations may lead to the first biomarker-specific, targeted therapy for HNSCC.
PARP Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • NOTCH1 (Notch 1) • PLK1 (Polo Like Kinase 1) • CASP3 (Caspase 3)
|
NOTCH1 mutation
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Mekinist (trametinib) • Gilotrif (afatinib) • Aliqopa (copanlisib) • volasertib (NBL-001) • Pozenveo (poziotinib) • BI2536 • bimiralisib (PQR309) • sapitinib (AZD8931)
almost4years
Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response. (PubMed, J Transl Med)
The findings reveal heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells.
Journal
|
EGFR (Epidermal growth factor receptor) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • CXCL10 (Chemokine (C-X-C motif) ligand 10)
|
IFNG elevation
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Erbitux (cetuximab) • gefitinib • sapitinib (AZD8931)
almost4years
The 3D Genomic Landscape of Differential Response to EGFR/HER2 Inhibition in Endocrine-Resistant Breast Cancer Cells. (PubMed, Biochim Biophys Acta Gene Regul Mech)
Our study has provided significant insights into our understanding of 3D genomic landscape changes in response to EGFR/HER2 Inhibition in endocrine-resistant breast cancer cells. Our data provides a rich resource for further evaluating chromatin structural responses to EGFR/HER2 targeted therapies in endocrine-resistant breast cancer cells. Our analyses suggest that these alterations of chromatin structures and transcriptional programs may provide new avenues for intervention or designing of patient selection for targeted endocrine treatment.
Journal
|
EGFR (Epidermal growth factor receptor)
|
gefitinib • lapatinib • tamoxifen • sapitinib (AZD8931)
4years
Sapitinib Reverses Anticancer Drug Resistance in Colon Cancer Cells Overexpressing the ABCB1 Transporter. (PubMed, Front Oncol)
Sapitinib significantly increased the efficacy of paclitaxel and doxorubicin in ABCB1 overexpressing cells without altering the expression or the subcellular location of the ABCB1 transporter. The docking study indicated that sapitinib interacted with the efflux site of ABCB1 transporter by π-π interaction and two hydrogen bonds. In conclusion, our study suggests that sapitinib surmounts MDR mediated by ABCB1 transporter in cancer cells.
Journal
|
EGFR (Epidermal growth factor receptor) • ABCB1 (ATP Binding Cassette Subfamily B Member 1)
|
ABCB1 overexpression
|
paclitaxel • doxorubicin hydrochloride • sapitinib (AZD8931)
4years
Exploring the radiosensitizing potential of AZD8931: a pilot study on the human LoVo colorectal cancer cell line. (PubMed, Int J Radiat Biol)
This radiosensitizing action by AZD8931 mainly occurred by markedly reducing cell cycle progression into S phase, the most radioresistant phase of cell cycle, secondly by inducing apoptosis and reducing clonogenic survival. Our results show that AZD8931 increases IR efficacy in LoVo cells, suggesting that it works as a potent radiosensitizer, even more efficient than Gefitinib and Cetuximab, opening new pathways of investigation for further in vitro and in vivo studies aimed at confirming its potential to improve local radiotherapy in CRC.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
|
Erbitux (cetuximab) • gefitinib • sapitinib (AZD8931)
4years
ErbB3, a possible prognostic factor of head and neck squamous cell carcinoma. (PubMed, Oral Surg Oral Med Oral Pathol Oral Radiol)
ErbB3 overexpression predicts a poor clinical outcome. Sapitinib was shown to be an effective inhibitor in the HNSCC cell line and animal models of cancer but with no statistical significance. Further studies with larger groups are needed to better support these results.
Journal
|
EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
|
HER-2 overexpression • ERBB3 overexpression
|
sapitinib (AZD8931)
over4years
Functional RNAi Screens Define Distinct Protein Kinase Vulnerabilities in EGFR-Dependent HNSCC Cell Lines. (PubMed, Mol Pharmacol)
The inhibitory epidermal growth factor receptor (EGFR) antibody, cetuximab, is an approved therapy for head and neck squamous cell carcinoma (HNSCC)...Mechanistic target of rapamycin kinase (MTOR) and erythroblastosis oncogene B (ERBB)3 were identified as high-ranking essential kinase hits in the HNSCC cell lines. MTOR dependency was confirmed by distinct short hairpin RNAs (shRNAs) and high sensitivity of the cell lines to AZD8055, whereas ERBB3 dependency was validated by shRNA-mediated silencing...As validation, distinct mitogen-activated protein kinase kinase (MEK) inhibitors yielded synergistic growth inhibition when combined with the EGFR inhibitors, gefitinib and AZD8931...SIGNIFICANCE STATEMENT: Many cancers are driven by non-mutated receptor tyrosine kinase co-activation networks that defy full inhibition with single targeted drugs. This study identifies ERBB3 as an essential protein kinase in EGFR-dependent HNSCC cell lines and a synthetic lethal interaction with the ERK MAPK pathway that provides a rationale for combining pan-ERBB and MAPK inhibitors as a therapeutic approach in subsets of HNSCC.
Journal
|
EGFR (Epidermal growth factor receptor)
|
Erbitux (cetuximab) • gefitinib • sirolimus • AZD8055 • sapitinib (AZD8931)
over4years
Synergistic Effect of Novel EGFR Inhibitor AZD8931 and p38α siRNA in Lung Adenocarcinoma Cancer Cells. (PubMed, Anticancer Agents Med Chem)
The results of this study indicated that p38 α and EGFR might play an important role in the development and growth of lung cancer and might be a potential therapeutic target for treatment of lung cancer.
Journal
|
HER-2 (Human epidermal growth factor receptor 2)
|
sapitinib (AZD8931)
over4years
[VIRTUAL] Translational analysis of esophageal adenocarcinoma (EAC) patients treated with oxaliplatin and capecitabine (Xelox) +/- the dual ErbB inhibitor AZD8931 in the DEBIOC study. (ASCO 2020)
We report the use of a novel software tool to apply 92 gene expression signatures to EAC biopsy and resection specimens from the DEBIOC trial to provide insight into mechanisms of action. Neoadjuvant treatment was associated with a reduction in DDR deficiency and an increase in angiogenesis and EMT signatures whilst a reduction in EGFR, Her2 and AKT pathways was noted with AZD8931 treatment. Research Funding: AstraZeneca, Other Government Agency, Cancer Research UK, OGcancerNI, Wellcome Trust
Clinical • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2)
|
HER-2 expression
|
capecitabine • oxaliplatin • sapitinib (AZD8931)